Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

BACKGROUND: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. METHODS: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. FINDINGS: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10-8; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10-9; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10-8; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10-13). INTERPRETATION: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. FUNDING: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research.

Evaluation of baseline F-18 FDG positron emission tomography in the diagnosis and assessment of giant cell arteritis.

Background/aim: The aim of this study is to evaluate the baseline F18-FDG PET/CT findings of individuals diagnosed with giant cell arteritis (GCA) and to explore its association with clinical findings and classification criteria. Materials and methods: We analysed data from patients who underwent F18-FDG PET/CT scans to investigate large vessel (LV) involvement between 2010 and 2019. Only patients with a clinical diagnosis of GCA and at least 6 months of follow-up were included. We compared initial clinical features and laboratory findings based on the presence of LV vasculitis on PET/CT and the maximum standard uptake value (SUVmax) of vascular territories. Results: Twenty-nine patients (median age at diagnosis: 70, F/M: 24/5) were included in the study. Among them, 21 patients (72.4%) presented with cranial symptoms, while 8 patients (27.5%) had isolated LV-GCA. Twenty-two patients (75.9%) met the ACR/EULAR 2022 GCA classification criteria. LV vasculitis was detected on PET/CT in 23 patients (79.3%). A positive correlation was observed between SUVmax in the thoracic aorta and both CRP and ESR levels (r = 0.50, p = 0.026 and r = 0.63, p = 0.002, respectively). PET/CT positive patients were found to be younger (p = 0.016) and more frequently female (p = 0.017). They also exhibited fewer headaches (56.5% vs. 100%, p = 0.04), experienced fewer flares during follow-up (p = 0.03), and had a lower cumulative glucocorticoid dose at the 6th month (p = 0.036). Comparison of PET/CT-positive patients (n = 23) based on the fulfilment of the ACR/EULAR 2022 classification criteria revealed that patients who met these criteria were older (p = 0.02) and had significantly lower CRP levels at diagnosis (p = 0.02). Conclusion: The performance of F18-FDG PET/CT in diagnosing LV involvement in GCA is favourable, and the severity of FDG uptake in the vessel wall correlates with the acute phase response. Patients with extracranial involvement on PET/CT exhibit distinct features, including a younger age and female predominance. Additionally, these patients appear to experience fewer relapses and require lower doses of glucocorticoids. However, the clinical significance of PET/CT in patients who met ACR/EULAR classification criteria, predominantly consisting of patients with ischemic cranial symptoms, could not be determined in our study.

Análisis coste/efectivo del diagnóstico de la arteritis de la temporal / Cost-effectiveness analysis of the diagnosis of temporal arteritis

La arteritis de la temporal (AT) es la forma más frecuente de vasculitis sistémica, su diagnóstico está basado en criterios propuestos por el Colegio Americano de Reumatología (1990), y su tratamiento son corticoides a dosis elevadas. Nuestro objetivo es valorar el gasto del diagnóstico de la AT, y secundariamente análisis coste/efectivo de distintas estrategias diagnósticas (clínica, biopsia, eco-Doppler) y terapéuticas (suspensión del corticoide). Material y método: Estudio observacional, retrospectivo de pacientes con AT (2012-2021). Se recogieron datos demográficos, comorbilidades, signos y síntomas sugestivos de AT. Se diagnosticó AT con una puntuación ≥3 según los criterios del American College of Reumatology (ACR-SCORE). Se analizaron los gastos del diagnóstico y modificación de tratamiento. Resultados: Setenta y cinco pacientes, mediana edad 77 (6-87) años. Cefalea, dolor temporal y claudicación mandibular fueron significativos para el diagnóstico de AT. Los pacientes con halo en eco-Doppler y biopsia positiva, presentaron elevación de VSG y PCR de forma significativa en comparación con los pacientes que no. El gasto diagnóstico de AT fue de 414,7€/paciente. Si empleamos ACR-SCORE≥3-eco-Doppler serían 167,2€/paciente (ahorro del 59,6%) y ACR-SCORE≥3-biopsia 339,75€/paciente (ahorro del 18%). Si se retiraba corticoide y se realizaba biopsia hubiesen sido 21,6€/paciente (ahorro del 94,7%), si se retiraba corticoide y se realizaba eco-Doppler hubiesen sido 10,6€/paciente (ahorro del 97,4%). Conclusiones: Cefalea, dolor temporal y claudicación mandibular son predictores de AT. La elevación de VSG y PCR son predictores de biopsia positiva y presencia de halo en la ecografía.El empleo de ACR-SCORE≥3 con eco-Doppler o con biopsia, y con suspensión del corticoide son coste/efectivos.(AU)

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, Doppler ultrasound) and therapeutic strategies (corticosteroid suspension).Material and method: Observational, retrospective study has been carried out on patients with TA (2012–2021). Demographic data, comorbidities, signs and symptoms suggestive of TA were collected. TA was diagnosed with a score ≥3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. Results: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not.: The cost of the TA diagnosis was 414.7 euros/patient. If we use ACR-SCORE≥3-echodoppler it is 167.2 €/patient (savings 59.6%) and ACR-SCORE≥3-biopsy 339.75 €/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 €/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 €/patient (97.4% savings).Conclusions: Headache, temporary pain and jaw claudication are predictors of TA. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE≥3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.(AU)

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 195 GCA patients.

OBJECTIVES: Giant cell arteritis (GCA) is one of the most common forms of vasculitis. There is an abundance of studies which are conducted in a randomised controlled trial setting but limited with respect to cohort size and follow-up time. GeVas is the first large-scale registry for vasculitides in German-speaking countries that enables to evaluate this rare disease. Herein we focus on the subgroup of GCA patients including follow-up data up to one year. METHODS: GeVas is a prospective, web-based, multicentre registry for the documentation of organ manifestations, outcomes, and therapy regimens in vasculitides. Recruitment started in June 2019. By April 2023, 15 centres were initiated and have started to enrol patients. RESULTS: After 4 years, 195 GCA-patients were included in the registry, of which 64% were female and 36% were male. The average age was 76 years at the time of recruitment (IQR=69-82). Seventy-nine percent were included in the registry because of a newly diagnosed GCA and 21% because of a relapse. At the first assessment most of the patients (89%) described general symptoms. Thirty-one percent stated ocular symptoms. Cranial symptoms were documented in 78% of the cases. All patients were documented with immunosuppressive treatment at start, of whom 95% received prednisolone, 16% cyclophosphamide, 20% methotrexate, and 48% tocilizumab. After three months 62% and after one year 91% of the patients achieved remission. CONCLUSIONS: Regarding demographics, clinical manifestations and diagnostics, our study showed a similar composition compared to other studies. However, our data differed in terms of treatment regimens.

Re: Epidemiology of giant cell arteritis in Waikato, Aotearoa New Zealand.

The interest in epidemiological data on giant cell arteritis (GCA) increased both in New Zealand and in Latin America, resulting in updated articles like those here commented. Of more relevance are two very recent contributions by van Dantzig et al. with novel conclusive findings from their evaluations on GCA performed in the region of Waikato. The authors emphasised that the diagnosis of GCA remained stable in this region from 2014 to 2022, being uncommon among Maori, Pacific peoples and Asian ethnic groups. Short comments on some literature data from Argentina, Brazil, Colombia, Peru and Mexico about the systemic arteritis are here addressed to show the Latin American view. The authors strongly believe that this kind of report may enhance the general interest on diagnostic and management issues related to this very important systemic vasculitis.

Myocardial infarction in a population-based cohort of patients with biopsy-confirmed giant cell arteritis in southern Sweden.

OBJECTIVES: To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA). METHODS: MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population. RESULTS: The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95% CI 2.2 to 3.6). CONCLUSIONS: The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA.

Giant Cell Arteritis. / Riesenzellarteriitis.

Giant cell arteritis (GCA) is the most common primary vasculitis and is associated with potential bilateral blindness. Neither clinical nor laboratory evidence is simple and unequivocal for this disease, which usually requires rapid and reliable diagnosis and therapy. The ophthalmologist should consider GCA with the following ocular symptoms: visual loss or visual field defects, transient visual disturbances (amaurosis fugax), diplopia, eye pain, or new onset head or jaw claudication. An immediate ophthalmological examination with slit lamp, ophthalmoscopy, and visual field, as well as color duplex ultrasound of the temporal artery should be performed. If there is sufficient clinical suspicion of GCA, corticosteroid therapy should be initiated immediately, with prompt referral to a rheumatologist/internist and, if necessary, temporal artery biopsy should be arranged. Numerous developments in modern imaging with colour duplex ultrasonography, MRI, and PET-CT have the potential to compete with the classical, well-established biopsy of a temporal artery. Early determination of ESR and CRP may support RZA diagnosis. Therapeutically, steroid-sparing immunosuppression with IL-6 blockade or methotrexate can be considered. These developments have led to a revision of both the classification criteria and the diagnostic and therapeutic recommendations of the American College of Rheumatologists and the European League against Rheumatism, which are summarised here for ophthalmology.

Cranial involvement in giant cell arteritis.

Since its first clinical description in 1890, extensive research has advanced our understanding of giant cell arteritis, leading to improvements in both diagnosis and management for affected patients. Imaging studies have shown that the disease frequently extends beyond the typical cranial arteries, also affecting large vessels such as the aorta and its proximal branches. Meanwhile, advances in comprehending the underlying pathophysiology of giant cell arteritis have given rise to numerous potential therapeutic agents, which aim to minimise the need for glucocorticoid treatment and prevent flares. Classification criteria for giant cell arteritis, as well as recommendations for management, imaging, and treat-to-target have been developed or updated in the last 5 years, and current research encompasses a broad spectrum covering basic, translational, and clinical research. In this Series paper, we aim to discuss the current understanding of giant cell arteritis with cranial manifestations, describe the clinical approach to this condition, and explore future directions in research and patient care.

Large vessel giant cell arteritis.

Giant cell arteritis is the principal form of systemic vasculitis affecting people over 50. Large-vessel involvement, termed large vessel giant cell arteritis, mainly affects the aorta and its branches, often occurring alongside cranial giant cell arteritis, but large vessel giant cell arteritis without cranial giant cell arteritis can also occur. Patients mostly present with constitutional symptoms, with localising large vessel giant cell arteritis symptoms present in a minority of patients only. Large vessel giant cell arteritis is usually overlooked until clinicians seek to exclude it with imaging by ultrasonography, magnetic resonance angiography (MRA), computed tomography angiography (CTA), or [18F]fluorodeoxyglucose-PET-CT. Although the role of imaging in treatment monitoring remains uncertain, imaging by MRA or CTA is crucial for identifying aortic aneurysm formation during patient follow up. In this Series paper, we define the large vessel subset of giant cell arteritis and summarise its clinical challenges. Furthermore, we identify areas for future research regarding the management of large vessel giant cell arteritis.

Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Cost-effectiveness analysis of the diagnosis of temporal arteritis.

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, doppler ultrasound) and therapeutic strategies (corticosteroid suspension). MATERIAL AND METHOD: Observational, retrospective study has been carried out on patients with AT (2012-2021). Demographic data, comorbidities, signs and symptoms suggestive of AT were collected. AT was diagnosed with a score ≥ 3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. RESULTS: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not. The cost of the AT diagnosis was 414.7 euros/patient. If we use ACR-SCORE ≥ 3-echodoppler it is 167.2 є/patient (savings 59.6%) and ACR-SCORE ≥ 3-biopsy 339.75 є/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 є/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 є/patient (97.4% savings). CONCLUSIONS: Headache, temporary pain and jaw claudication are predictors of AT. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE ≥ 3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.

[Challenges and perspectives for the treatment of giant cell arteritis]. / Défis et perspectives pour le traitement de l'artérite à cellules géantes.

Early diagnosis and prompt initiation of treatment are crucial to avoid severe complications in giant cell arteritis (GCA). The European Alliance of Associations for Rheumatology (EULAR) recommendations for the use of imaging in large vessel vasculitis have helped better define the role of different techniques for diagnosing and monitoring the disease. Regarding the treatment, corticosteroids remain the standard, and tocilizumab is the preferred corticosteroid-sparing treatment. New corticosteroid-sparing treatments and "ultra-light" corticosteroid usage regimens are also under study and could represent valid therapeutic alternatives in the future.

L'artérite à cellules géantes est une vascularite pouvant avoir de graves conséquences, telles que la cécité. Le diagnostic et l'introduction d'un traitement dans les meilleurs délais sont cruciaux pour éviter ces complications. Les recommandations de l'Alliance des associations européennes pour la rhumatologie (EULAR) sur l'utilisation de l'imagerie dans les vascularites des gros vaisseaux ont permis de mieux définir le rôle des différentes techniques pour le diagnostic et le suivi de la maladie. Concernant le traitement, les corticostéroïdes restent la référence et le tocilizumab le traitement d'épargne cortisonique de choix. De nouveaux traitements d'épargne cortisonique et des schémas d'utilisation des glucocorticoïdes à doses « ultra-faibles ¼ sont aussi en phase d'étude et pourraient représenter de futures alternatives thérapeutiques.

Current Insights into Tissue Injury of Giant Cell Arteritis: From Acute Inflammatory Responses towards Inappropriate Tissue Remodeling.

Giant cell arteritis (GCA) is an autoimmune disease affecting large vessels in patients over 50 years old. It is an exemplary model of a classic inflammatory disorder with IL-6 playing the leading role. The main comorbidities that may appear acutely or chronically are vascular occlusion leading to blindness and thoracic aorta aneurysm formation, respectively. The tissue inflammatory bulk is expressed as acute or chronic delayed-type hypersensitivity reactions, the latter being apparent by giant cell formation. The activated monocytes/macrophages are associated with pronounced Th1 and Th17 responses. B-cells and neutrophils also participate in the inflammatory lesion. However, the exact order of appearance and mechanistic interactions between cells are hindered by the lack of cellular and molecular information from early disease stages and accurate experimental models. Recently, senescent cells and neutrophil extracellular traps have been described in tissue lesions. These structures can remain in tissues for a prolonged period, potentially favoring inflammatory responses and tissue remodeling. In this review, current advances in GCA pathogenesis are discussed in different inflammatory phases. Through the description of these-often overlapping-phases, cells, molecules, and small lipid mediators with pathogenetic potential are described.

Giant cell arteritis: insights from a monocentric retrospective cohort study.

Giant cell arteritis (GCA), more common in Northern European populations, has limited data in Arabcountries. Our study reports GCA's clinical manifestations in Jordan and reviews published research on GCA across Arab nations. In this retrospective analysis, GCA patients diagnosed from January 2007 to March 2019 at a Jordanian academic medical center were included through referrals for temporal artery biopsy (TAB). A comprehensive search in PubMed, Scopus, and the DOAJ (Directory of Open Access Journals) databases was conducted to identify all relevant English-language manuscripts from Arab countries on GCA without time limitations. Among 59 diagnosed GCA patients, 41 (69.5%) were clinically diagnosed with a negative TAB, and 19 (30.5%) had a positive result. Females comprised 74.6% (n = 44) with 1:3 male-female ratio. The mean age at diagnosis was 67.3 (± 9.5) years, with most presenting within two weeks (n = 40, 67.8%). Headache was reported by 54 patients (91.5%). Elevated ESR occurred in 51 patients (78%), with a mean of 81 ± 32.2 mm/hr. All received glucocorticoids for 13.1 ± 10 months. Azathioprine, Methotrexate, and Tocilizumab usage was 15.3% (n = 9), 8.5% (n = 5), and 3.4% (n = 2), respectively. Remission was observed in 57.6% (n=34), and 40.7% (n = 24) had a chronic clinical course on treatment. Males had higher biopsy-based diagnoses (p = .008), and biopsy-diagnosed patients were older (p = .043). The literature search yielded only 20 manuscripts originating in the Arab world. The predominant study types included case reports and retrospective analyses, with only one case series and onecase-control study.

APDS patients with immune-complex vasculitis and resolution with leniolisib.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity with heterogeneous clinical manifestations of infections, immune dysregulation, autoimmunity; lymphoproliferation; and malignancy. Immune complex-mediated vasculitides have not yet been described in APDS patients. Here we offer a case series of three patients with APDS who have refractory IgA vasculitis (also called Henoch-Schönlein purpura), a form of immune complex-mediated vasculitis that activates complement and attracts neutrophils, macrophages and eosinophils to cause local tissue injury. Leniolisib is an inhibitor of PI3K p110δ and an FDA-approved treatment for APDS. IgA vasculitis resolved upon treatment with leniolisib. Patients with immune dysregulation including IgA vasculitis should be screened for APDS.

Incidence and clinical manifestations of giant cell arteritis in Spain: results of the ARTESER register.

OBJECTIVE: This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season. METHODS: We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season. RESULTS: We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80-84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients. CONCLUSIONS: This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.